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BACHELOR OF PHARMACY
UNDERGUIDANCEOF
Mr.Nilesh R. Sisode
Asst.Professor
Department of Pharmaceutics
DCSsA.R.ACOLLEGE OFPHARMACY,NAGAON,DHULE
j
2021-22
CERTIFICATE BY PRINCIPAL
Nilesh.R.Sisode.
Place: Dhule
Date:
Dr.RajendraD.Wagh
Principal
DCS’s A.R.A. College of
Pharmacy, Nagaon,
Dhule
DCSsA.R.ACOLLEGE OFPHARMACY,NAGAON,DHULE
COMPUTERAIDEDDRUGDESIGN 2
Date: / /2021
Place:Dhule Marathe Latikesh Subhash
Marathe Hemant Nivrutti
COMPUTERAIDEDDRUGDESIGN 3
DECLARATION BY GUIDANCE
Date: / /2021
ACKNOWLEDGEMENT
INDEX
1. ABSTRACT
2.DRUG DESIGN
3.BACKGROUND
4.DRUGDESIGNTYPE
5.COMPUTER AIDED DRUG DESIGN
6.OBJECTIVE
7.DRUGDISCOVERY
8.COMPUTATIONALTOOLS
9.APPLICATION
10.ADVANTAGES & DISADVANTAGES
COMPUTERAIDEDDRUGDESIGN 6
ABSTRACT
DRUG DESIGN
INTRODUCTION
Drug design, sometimes referred to as rational
drugdesign or more simply rational design, is the
inventiveprocess of finding new medications based on
theknowledge of a biological target. The drug is
mostcommonly an organic small molecule that activates
orinhibits the function of a biomolecule such as aprotein,
which in turn results in a therapeutic benefitto the
patient. In The most basic sense, drug designinvolves the
design of small molecules that are Complementary in
shape and charge to the bimolecular target with which
they interact and therefore will bind to it.Drug design
frequently but
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COMPUTERAIDEDDRUGDESIGN 10
Background
Typically a drug target is a key molecule Involved in
aParticular metabolic or signaling pathway that isspecific
to a disease condition or pathology or To theinfectivity or
survival of a microbial pathogen. Someapproaches
attempt to inhibit the Functioning of thepathway in the
diseased state by causing a keymolecule to stop
functioning. Drugs may be designedthat bind to the active
region and inhibit this keymolecule. Another Approach
may be to enhance thenormal pathway by promoting
specific molecules inthe normal Pathways that may have
been affected inthe diseased state. In addition, these
drugs should alsobedesignedsoasnottoaffect
anyotherimportant
COMPUTERAIDEDDRUGDESIGN 11
“off-target”moleculesor antiTargetsthatmaybe
similarin appearancetothetargetmolecule.
Therearetwomajortypesofdrugdesign.Thefirstisreferred
to as ligand-based drug design And thesecond,structure-
baseddrugdesign.
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TYPES
1. ligand-baseddrugdesign
2. structure-baseddrugdesign
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Ligand-based
“Finding”ligandsforagivenreceptor,whichisusuallyreferredasDa
tabasesearching.
COMPUTERAIDEDDRUGDESIGN 17
FlowchartofaUsualClustering
AnalysisforStructure-BasedDrugDesign.
Activesite identification
Ligandfragmentlink
Flowchartforstructure-baseddrugdesign
COMPUTERAIDEDDRUGDESIGN 20
Examples
A particular example of rational drug design involves
the use of three-dimensional information about
biomolecules obtained from such techniques as X-ray
crystallography and NMR Spectroscopy. Computer-
aided drug design in particular becomes much more
tractable whenthere’s a high-resolution structure of a
target protein bound to a potent ligand. This
approach to Drug discovery is sometimes referred to
asstructure-based drug design. The first unequivocal
Example of the application of structure- based drug
design leading to an approved drug is theCarbonic
anhydrase inhibitor dorzolamide, which was
approved in 1995.Another important casestudy in
rational drug design is imagine, a tyrosine kinase
inhibitor Designed specifically for the
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o Zanamivir,anantiviraldrug
COMPUTER-AIDEDDRUGDESIGN
INTRODUCTION
OBJECTIVE
change from:-
Random screening against disease assay
Natural product, synthetic chemicals
Rational drug design and testing
Speed upscreening process
Efficient screening
Denovo design
Fails drugs fast
COMPUTERAIDEDDRUGDESIGN 29
DRUGS DISCOVERY
Database:-
o Zincdatabase
o C h embl
o JchemforExcel
o ProteindataBank
o Bindingmoad
o PDBBind
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Drawtools:-
o Chemdraw
o Marvinsketch
o Chemsketch
o Marvinmolecule editor
o Chemwriter.
COMPUTERAIDEDDRUGDESIGN 43
Molecularmodelling :-
o CHARMM
o GROMACS
o AMBER
o SWISSPARAM
o CHARMM.org
o CHARMM-GUI
COMPUTERAIDEDDRUGDESIGN 44
APPLICATION
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DCSsA.R.ACOLLEGEOFPHARMACY,NAGAON,DHULE
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DCSsA.R.ACOLLEGEOFPHARMACY,NAGAON,DHULE